Treatment options in type-2 low asthma
Treatment options in type-2 low asthma
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DOI：
10.1183/13993003.00528-2020
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发表时间：
2021-01-01
影响因子：
24.3
通讯作者：
Brusselle, Guy G.
中科院分区：
文献类型：
--
作者：
Hinks, Timothy S. C.;Levine, Stewart J.;Brusselle, Guy G.
针对IgE或2型细胞因子IL-4、IL-5和IL-13的单抗被证明在分别减少严重过敏性哮喘和嗜酸性哮喘患者的恶化和症状方面非常有效。然而，这些疗法不适合重症哮喘诊所30%-50%的非过敏性、非嗜酸性、“2型低”哮喘患者。这些患者构成了一种重要而常见的临床哮喘表型，由不同的、但鲜为人知的病理生物学机制驱动。在这篇综述中，我们描述了2型低度哮喘的异质性和临床特征，并总结了其潜在的病理生物学机制，包括中性粒细胞的呼吸道炎症，通常与吸烟、肥胖和职业暴露有关，可能由持续的细菌感染和最近描述的IL-6途径的激活所驱动。我们回顾了可识别和解决的特定可治疗特征的现有治疗选择背后的证据基础。我们特别关注重症哮喘而不是难治性哮喘，关于呼吸道细菌感染鉴定的新数据，长期使用低剂量大环内酯类药物的越来越多的证据基础，对支气管热成形术的关键评估，以及在2型低度疾病中使用生物制剂的证据。最后，我们综述了正在进行的其他途径的研究，包括肿瘤坏死因子、IL-17、溶血素、载脂蛋白、I型间质、IL-6和肥大细胞。我们认为，2型低血压病往往提供了识别和治疗可治疗的临床问题的机会；它目前是一个快速发展的领域，具有开发新的靶向疗法的潜力。
Monoclonal antibodies targeting IgE or the type-2 cytokines interleukin (IL)-4, IL-5 and IL-13 are proving highly effective in reducing exacerbations and symptoms in people with severe allergic and eosinophilic asthma, respectively. However, these therapies are not appropriate for 30-50% of patients in severe asthma clinics who present with non-allergic, non-eosinophilic, "type-2 low" asthma. These patients constitute an important and common clinical asthma phenotype, driven by distinct, yet poorly understood pathobiological mechanisms. In this review we describe the heterogeneity and clinical characteristics of type-2 low asthma and summarise current knowledge on the underlying pathobiological mechanisms, which includes neutrophilic airway inflammation often associated with smoking, obesity and occupational exposures and may be driven by persistent bacterial infections and by activation of a recently described IL-6 pathway. We review the evidence base underlying existing treatment options for specific treatable traits that can be identified and addressed. We focus particularly on severe asthma as opposed to difficult-to-treat asthma, on emerging data on the identification of airway bacterial infection, on the increasing evidence base for the use of long-term low-dose macrolides, a critical appraisal of bronchial thermoplasty, and evidence for the use of biologics in type-2 low disease. Finally, we review ongoing research into other pathways including tumour necrosis factor, IL-17, resolvins, apolipoproteins, type I interfemns, IL-6 and mast cells. We suggest that type-2 low disease frequently presents opportunities for identification and treatment of tractable clinical problems; it is currently a rapidly evolving field with potential for the development of novel targeted therapeutics.